Search Results (85)

Background/Objectives: This study aimed to investigate the effect of pancreatic ductal adenocarcinoma (PDAC) on the alterations in red blood cell aggregation related to angiogenesis and hypoxia markers. Methods: We studied 31 patients with confirmed PDAC. The aggregation of red blood cells (RBCs) was evaluated using a Laser-assisted Optical Rotational Cell Analyzer (LORCA). Serum vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) levels were measured using ELISA. We estimated the following parameters specific to the aggregation process: the aggregation index (AI), the aggregation half-time (t_1/2), and the threshold shear rate (γ_thr). Results: All measured RBC aggregation parameters among PDAC subjects differed from those in the controls. The AI (p < 0.05) and γ_thr (p < 0.005) were significantly higher in the PDAC group, whereas t_1/2 (p < 0.01) and AMP (p < 0.001) were significantly lower compared to the control group. The levels of VEGF (p < 0.0001) and HIF-1α (p < 0.0001) were significantly higher in the PDAC group than in the control group. There were significant correlations between RBC aggregation parameters and VEGF and HIF-1α. Multivariate analyses further identified t_1/2 (p < 0.01) and γ_thr (p < 0.05) as independent predictors for VEGF. For HIF-1α, t_1/2 (p < 0.05) was confirmed as an independent predictor. Conclusions: The results suggest, but do not demonstrate, a direct pathophysiological link between PDAC-associated hypoxia/angiogenesis and erythrocyte aggregation. Further studies are needed because the relationship linking PDAC to these aggregation indices is unclear. Full article

Accurate assessment of blood viscosity and red blood cell (RBC) aggregation under continuous flow is important for hemorheological analysis. However, simultaneous measurement remains challenging because both properties are influenced by flow conditions and RBC sedimentation. In this study, a microfluidic method is developed for the simultaneous measurement of blood viscosity and RBC aggregation index (AI) during continuous blood delivery from a driving syringe. The proposed device consists of a viscosity-sensing channel for viscosity measurement and aggregation-sensing channel for AI evaluation. The effects of flow rate, hematocrit, suspension medium, and syringe on–off operation are systematically investigated. Blood viscosity and AI are strongly affected by these factors, and transient flow interruption enhances RBC sedimentation in the syringe, thereby altering hemorheological properties. The proposed method is further used to evaluate thermally exposed RBCs, which reduce RBC aggregation and suppress RBC sedimentation when compared with control blood. At higher exposure temperatures and longer exposure times, blood viscosity and AI remain nearly constant over time, indicating minimal contribution of damaged RBCs to RBC sedimentation. These results demonstrate that the proposed method enables reliable simultaneous evaluation of blood viscosity and RBC aggregation and could be regarded as useful for detecting functional alterations of RBCs under continuous-flow conditions. Full article

This study investigates the effects of a novel marine byproduct oil extracted from the cephalopod Nototodarus sloani (Arrow squid) on human platelets and red blood cells (RBCs). The oil was produced using enzyme-assisted extraction under varying pH conditions without further refining. The level of oxidation of the different oils was determined. Hemocompatibility and oxidative effects were evaluated after 24 h of incubation at physiological and fever-like conditions. Hemolysis levels varied with extraction conditions and with the amount of oil in contact with the cells. Oils extracted using 0.5% Alcalase^® and 1% Protamex^{TM ®} at pH 5.9 demonstrated superior hemocompatibility. Intracellular reactive oxygen species (ROS) levels presented a dose-dependent increase, with higher levels observed in oils extracted at a higher pH. Although there was no direct correlation between hemolysis rate, ROS levels and oxidation, the less oxidized oils presented lower ROS formation and better hemocompatibility. Additionally, the oils exhibited a strong anticoagulant effect and low IC₅₀ values against TRAP-6-induced platelet aggregation. These findings highlight the potential of Nototodarus sloani as a source of bioactive compounds, providing initial evidence of potential cardiovascular benefits and resource valorization, underlining the importance of extraction conditions in determining the biological properties of marine byproduct oils. Full article

Long COVID is associated with persistent fatigue, exercise intolerance, and microcirculatory dysfunction. Altered red blood cell (RBC) rheology, including impaired deformability and increased aggregation, may contribute to these symptoms, yet the effects of exercise interventions remain unclear. This longitudinal pilot study tested whether an individualized, symptom-responsive exercise program improves RBC rheology in Long COVID. A total of 170 (110 f/60 m) participants entered a five-phase training protocol; 15 completed all phases and formed a predefined finisher subgroup. RBC aggregation and deformability, hematological parameters, and coagulation- and iron-related markers were assessed across phases; RBC morphology was additionally analyzed in finishers at baseline and completion. In the total cohort, aggregation indices decreased across training phases, accompanied by prolonged aggregation half-time, while hematological, coagulation, and iron markers remained largely unchanged. The deformability changes were not uniform in the full cohort; however, finishers showed a deformability shift after completion. Importantly, morphologically abnormal RBC decreased in finishers, and these changes correlated with deformability, suggesting that improved rheology is linked to reduced RBC abnormalities. Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits. Full article

For effectively assessing blood, red blood cell (RBC) aggregation and blood viscosity have been measured in microfluidic environments. However, the previous methods still face several challenges (dead-volume loss, RBC sedimentation, hematocrit-sensitive blood velocity, and precise flow rate control). In this study, a novel method is suggested to resolve several issues. Air cavity (V_air = 250 μL) is secured above the blood column (at least 100 μL) loaded into a driving syringe. To probe RBC aggregation and blood viscosity, a microfluidic chip consists of a main channel ($\dot{\gamma }$ > 1000 s⁻¹) and an aggregation channel ($\dot{\gamma }$ < 50 s⁻¹). Blood is supplied into a microfluidic chip with two-step blood delivery (i.e., air compression for RBC aggregation, and syringe pump for blood viscosity). RBC aggregation index and blood viscosity are obtained from time-lapse image intensity and blood flow rate in both channels. As performance demonstrations, first, the measurement accuracy of fluid viscosity is validated with glycerin solution. Then, the present method is adopted to probe the difference in hematocrit and dextran concentration. At last, the proposed method is employed to detect heat-shocked RBCs (45~50 °C for 40 min). In conclusion, the proposed method has the ability to accurately measure substantial changes in RBCs or blood medium. Full article

Physical activity influences red blood cell (RBC) deformability and aggregation, which affect oxygen transport and performance. While regular training may enhance RBC properties, adaptations depend on exercise intensity, duration, and recovery. This study aimed to assess the impact of a 12-week core muscle training program on RBC deformability, aggregation, and aerobic capacity in military trainees. A total of 35 male volunteers were divided into a Training group (n = 17) and a Control group (n = 18). The intervention included dynamic stretching, core stabilization, and functional movement exercises. Spiroergometry tests, blood gas analysis, and hemorheological measurements were conducted before and after the program. Results showed no significant changes in body composition or aerobic capacity. RBC deformability slightly decreased after exercise in both groups, while RBC aggregation increased. Blood viscosity changes were more moderate in the Training group, suggesting potential adaptation. However, the training intensity may have been insufficient for significant hemorheological improvements. While regular physical activity can enhance RBC function, adequate intensity, recovery, and nutrition are essential for optimal adaptation. Individualized training strategies should consider these factors to maximize performance and hemorheological benefits. Full article

Aging is a complex biological process marked by progressive physiological decline with increasing vulnerability to diseases such as cardiovascular disorders, neurodegenerative conditions, and metabolic syndromes. Identifying reliable biomarkers of aging is essential for assessing biological age, predicting health outcomes, and guiding interventions to promote healthy aging. Among various candidate biomarkers, red blood cells (RBCs) offer a unique and accessible window into the aging process due to their abundance, finite lifespan, and responsiveness to systemic changes. This review examines the potential of RBCs as biomarkers of aging by exploring their age-associated morphological, functional, and biochemical alterations. Age-related reduction in key haematological parameters such as RBC count, haemoglobin concentration, and haematocrit, and increases in mean cell volume (MCV) and red cell distribution width (RDW), reflect underlying shifts in erythropoiesis and cellular turnover. Functional changes include reduced oxygen-carrying capacity, decreased deformability, diminished ATP release, and increased RBC aggregation, all of which may impair both macrocirculatory and microcirculatory flow and tissue oxygenation. Biochemically, aging RBCs exhibit altered membrane lipid and protein composition, reduced membrane fluidity, and diminished antioxidant and enzymatic activity, contributing to cellular senescence and clearance. Despite these promising indicators, challenges persist in establishing RBC parameters as definitive biomarkers of aging. Inter-individual and intra-individual variability and storage-related artifacts complicate their use. In conclusion, RBCs present a compelling, though currently underutilized, avenue for aging biomarker research. Further longitudinal validation and mechanistic research are essential to support the clinical utility of RBC parameters as biomarkers of aging. Full article

Antimicrobial peptides (AMPs) are a primary defense against pathogens. Here, we examined the interaction of two BP100 analogs, R²R⁵-BP100 (where Arg substitutes Lys 2 and 5) and R²R⁵-BP100-A-NH-C₁₆ (where an Ala and a C₁₆ hydrocarbon chain are added to the R²R⁵-BP100 C-terminus), with membrane models. Large unilamellar vesicles (LUVs) and giant unilamellar vesicles (GUVs) were prepared with the major lipids in Gram-positive (GP) and Gram-negative (GN) bacteria, as well as red blood cells (RBCs). Fluorescence data, dynamic light scattering (DLS), and zeta potential measurements revealed that upon achieving electroneutrality through peptide binding, vesicle aggregation occurred. Circular dichroism (CD) spectra corroborated these observations, and upon vesicle binding, the peptides acquired α-helical conformation. The peptide concentration, producing a 50% release of carboxyfluorescein (C₅₀) from LUVs, was similar for GP-LUVs. With GN and RBC-LUVs, C₅₀ decreased in the following order: BP100 > R²R⁵-BP100 > R²R⁵BP100-A-NH-C₁₆. Optical microscopy of GP-, GN-, and RBC-GUVs revealed the rupture or bursting of the two former membranes, consistent with a carpet mechanism of action. Using GUVs, we confirmed RBC aggregation by BP100 and R²R⁵-BP100. We determined the minimal inhibitory concentrations (MICs) of peptides for a GN bacterium (Escherichia coli (E. coli)) and two GP bacteria (two strains of Staphylococcus aureus (S. aureus) and one strain of Bacillus subtilis (B. subtilis)). The MICs for S. aureus were strain-dependent. These results demonstrate that Lys/Arg replacement can improve the parent peptide’s antimicrobial activity while increasing hydrophobicity renders the peptide less effective and more hemolytic. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

Red blood cell (RBC) aggregation and disaggregation are key factors in microcirculatory flow, and their disturbance can lead to alterations in the rheological properties of blood in disorders such as chronic lymphocytic leukemia (CLL). This study aimed to determine the critical shear rate required to fully disaggregate RBC aggregates using samples from healthy individuals, providing a reference point for evaluating pathological changes. Using a microfluidic system and software-image-based flow analysis, RBC disaggregation was assessed by the Aggregation-Area Indicator at a high shear rate (AAI_H) changes and the number of undestroyed aggregates. The defined critical shear rate at 446 s⁻¹ was applied to assess RBC disaggregation in CLL patients, both untreated and treated with Obinutuzumab/Venetoclax or Ibrutinib. CLL samples exhibited significantly elevated AAI_H values compared to controls, indicating a greater resistance to shear-induced dispersion. Although both treatments reduced the number of stable aggregates, neither therapy fully normalized RBC disaggregation to the levels observed in healthy controls. Moreover, there was a notable heterogeneity among Ibrutinib-treated patients, revealing different therapeutic effects on RBC rheology. These findings suggest alterations in the RBC rheology in CLL despite therapy and support the use of a shear-dependent disaggregation analysis as a complementary tool for understanding and monitoring CLL-related hematologic abnormalities. Full article

The biomechanical properties of blood are regarded as promising biomarkers for monitoring early-stage abnormalities and disease progression. To detect any changes in blood, it is necessary to measure as many rheological properties as possible. Herein, a novel method is proposed for measuring multiple rheological properties of blood using a microfluidic chip. The syringe pump turns off for 5 min to induce RBC (red blood cell) sedimentation in the driving syringe. RBC aggregation is determined by analyzing the time-lapse blood image intensity at stasis: I(t) = I₁ exp (−k₁t) + I₂ exp (−k₂t). RBC-rich blood and RBC-depleted blood are sequentially infused into the microfluidic chip. Based on blood pressure estimated with time-lapse blood velocity, blood viscosity is acquired with the Hagen–Poiseuille law. RBC sedimentation is quantified as RBC sedimentation distance (X_esr) and erythrocyte sedimentation rate (ESR). The proposed method provides a consistent viscosity compared with previous methods. Two of the four variables (I₁, I₂) exhibited a strong correlation with the conventional RBC aggregation index (AI). The indices X_esr and ESR showed consistent trends with respect to the blood medium and hematocrit. In conclusion, the proposed method is then regarded as effective for monitoring multiple rheological properties. Full article

Background: Physical activity in elderly adults reduces the risk of numerous diseases, enhances their quality of life, and improves their physical performance and overall strength. This study aimed to evaluate the effects of smovey^® exercise on morphological and rheological blood parameters in a group of women over 60 years of age. Methods: The study included 30 women aged 71.08 ± 6.41 years, with a control group of 15 age-matched women. Participants in the experimental group underwent a three-month smovey^® training program, consisting of two 45 min sessions per week. The control group did not engage in any regular physical activity. Blood samples were collected from the experimental group before and after the training period, while in the control group, blood was collected once. Results: After three months of smovey^® training, a statistically significant increase in red blood cell, hemoglobin, and platelet counts was observed. Smovey^® training also enhanced erythrocyte deformability at the lowest shear force. Conclusions: Smovey^® training leads to changes in the morphological properties of blood in elderly women, leading to increases in RBC, HGB, PLT, and MCHC indices. Additionally, smovey^® training improves erythrocyte deformability at a shear stress of 0.30 [Pa], reducing the half-time of complete aggregation. Full article

The response to exercise following a rest period may vary among horse breeds based on the importance of the hematological and hematochemical profiles of athletic horses. Ten Standardbred and ten Italian Saddlebred mares were subjected to a 4-week training program after a seasonal rest, and hematological parameters (red blood cells—RBCs; hemoglobin—Hb; hematocrit—Hct; platelets—PLTs; platelet aggregation—AG; aggregation slope—Slope; fibrinogen—Fb), as well as Albumin (Alb) and non-esterified fatty acids (NEFAs), were analyzed. Blood samples were obtained each week during the training program following a simulated exercise performed at T0 and T4 (T0pre-T0post; T1, T2, T3, and T4pre-T4post). A two-way ANOVA revealed an increase in all assessed parameters post vs. pre at T0 and T4 (p < 0.01) and a decrease in PLTs (p < 0.01) at T0 and T4 in both breeds. A significant effect of breed was observed, with higher values for RBCs and Hb at each time point (p < 0.001); Hct at T0 post, T2, T3, and T4 post; and NEFAs (p < 0.001) at T0 post and T4 post in Standardbred compared to Saddlebred horses. Positive correlations were identified among RBCs, Hb, Hct, PLTs, Alb, and NEFAs in both breeds and between AG and Slope in Saddlebred horses. Negative correlations were identified among AG and RBCs, Hb, Hct, PLTs, Alb, and NEFAs in Standardbred horses and for AG and Slope with RBCs, Hb, Hct, and PLTs in Saddlebred horses. A comparable reaction to training was observed in both breeds following the seasonal rest. Full article

Nature equipped red blood cells (RBCs) with diverse mechanical properties, which makes it possible to examine blood with different RBC properties (size, shape, aggregability, deformability). We investigated whether the shelf life of cow blood (stiff RBCs, low aggregability) is longer compared with pig blood (deformability/aggregability comparable to human) due to a delay in RBC clustering and decomposition. Blood was drawn from conscious pigs and cows in their familiar environment to reduce stress and stored 30 days at +7 °C. RBCs remained intact in cow samples whereas pig samples became hemolytic after day 20. White blood cells and platelets decreased with similar percentages in both species. Hematocrit (HCT) decreased due to RBC shrinking in bovine samples and due to RBC decay in porcine samples. Blood viscosity increased in both species although HCT decreased. In porcine samples, shear thinning decreased progressively, indicating a gradual loss of sample cohesion with storage. Yield stress and storage modulus decreased with hemolysis. In HCT-native cow samples, shear thinning, yield stress, and storage modulus showed high intraindividual variability, but the mean values did not change over the time course. In HCT-adjusted (38%) cow samples, solidification occurred after day 7, followed by a reduction in cohesion and shear thinning until the end of storage. Full article

Chronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton’s tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow. In this study, we applied a microfluidic device and a newly developed Software Image Flow Analysis to assess the extent of RBC aggregation in CLL patients and to elucidate the hemorheological effects of the commonly applied therapeutics Obinutuzumab/Venetoclax and Ibrutinib. The results revealed that, in RBC samples from untreated CLL patients, complex 3D clusters of large RBC aggregates are formed, and their number is significantly increased compared to healthy control samples. The application of the Obinutuzumab/Venetoclax combination did not affect this aspect of RBCs’ rheological behavior. In contrast, targeted therapy with Ibrutinib preserves the aggregation state of CLL RBCs to levels seen in healthy controls, demonstrating that Ibrutinib mitigates the alterations in the rheological properties of RBCs associated with CLL. Our findings highlight the alterations in RBC aggregation in CLL and the impact of different targeted therapies on RBCs’ rheological properties, which is critical for predicting the potential complications and side effects of CLL treatments, particularly concerning blood flow dynamics. Full article